1. Field of the Invention
This invention relates to a collagen-based composition for augmenting soft tissue repair, a collagen-based wound dressing and a collagen-based drug delivery system.
2. Background of the Invention
Collagen is the major connective tissue protein in animals. It has an extended history of use in the medical field primarily due to its ability to polymerize in vitro into strong fibers that can be fabricated into a number of forms. Collagen has been utilized for a variety of clinical purposes including wound treatment, hemostasis, and soft tissue augmentation. We have described these and other medical applications of collagen in a recent review. Pachence J. M., Berg R. A., and Silver F. H., "Collagen: Its Place in the Medical Device Industry", Med. Device & Diag. Ind., 9:49-55, 1987.
Soluble collagen has been used as a subcutaneous implant for repairing dermatological defects such as acne scars, glabellar furrows, excision scars and other soft tissue defects. Klein, A. W. J.Acad. Derm. 9:224-228 (1983); Knapp, T. R., Luck, E., and Daniels, J. R. J.Surg. Res. 23:96-105 (1977); and Kaplan, E. N., Falces, E., and Tolleth, H. Clinical Utilization of Injectable Collagen, Ann. Plast. Surg., 10:437-451 (1983). Although it appers that this implant is readily accepted, the repair of the defects is temporary and patients need additional treatment after 6 to 18 months. There were also a number of adverse tissue responses after utilization of soluble collagen. Castrow, F. F., and Krull, E. A. Injectable Collagen Implant--Update, J. Am. Acad. Dermatol. 9:889-893 (1983). Labow, T. A., and Silvers, D. N. Late Reactions at Zydern Skin Test Sites, Cutis 35:154--158 (1984) and Cohen, I. K. Peacock, E. E., and Chvapil, M. Editorial on Zyderm, Plast. Reconstr. Surg., 73:1 (1984).
Collagen has also been used in many forms as a wound dressing. The various forms of collagen wound dressings include collagen sponges such as described in Artandl U.S. Pat. No. 3,157,524 and Berg et al U.S. Pat. No. 4,320,201; and collagen/polymer film composites such as described in McKnight et al, U.S. Pat. No. 3,800,792. However, many of these dressings are not satisfactory for the various types of full thickness wounds. Collagen films and sponges do not readily conform to varied wound shapes. Further, some collagen wound dressings such as collagen films have poor fluid absorption properties and enhance the pooling of wound fluids.
The use of Type I collagen in a wound dressing has had limited success due to its reported limited application for epidermal cell support. It has been indicated that attachment factors such as laminin and Type IV collagen are necessary for optimal epidermal cell growth. Lillie, J .H., MacCullum, D. K., and Jepsen, A. In: Epithelial Messenchymal Interactions in Development, R. H. Sawyer and J. F. Fallon, eds., Praeger Scientific, N.Y. 1983, pp 99-111; Stanley, J. R. Foidart, J., Murray, J. C. Martin, G. D. and Katz, S. T. (1980) J. Invest. Dermatol. 74:54-58; and Kleinman, H. K., Klebe, R. J., and Martin, G. R. The Role of Collagen Matrices in Adhesion and Growth of Cell., J. Cell Biol. 88:473 (1981). Similarly, the presence of hyaluronic acid or fibronectin greatly improves the ability of the matrix to support fibroblast growth. (Doillon et al. (1987) Biomaterials 7:195-200).
It is, accordingly, among the objects of the present invention to provide an improved collagen-based wound dressing, and a method for augmenting soft tissue repair therewith.